Description
Description : Nasopharyngeal carcinoma (NPC) is a unique EBV-associated epithelial malignancy, showing highly invasive and metastatic
phenotype. Despite increasing evidence demonstrating the critical role of cancer stem-like cells (CSCs) in the maintenance
and progression of tumors in a variety of malignancies, the existence and properties of CSC in EBV-associated NPC are
largely unknown. Our study aims to elucidate the presence and role of CSCs in the pathogenesis of this malignant disease.
Sphere-forming cells were isolated from an EBV-positive NPC cell line C666-1 and its tumor-initiating properties were
confirmed by in vitro and in vivo assays. In these spheroids, up-regulation of multiple stem cell markers were found. By flow
cytometry, we demonstrated that both CD44 and SOX2 were overexpressed in a majority of sphere-forming C666-1 cells.
The CD44+SOX2+ cells was detected in a minor population in EBV-positive xenografts and primary tumors and considered
as potential CSC in NPC. Notably, the isolated CD44+ NPC cells were resistant to chemotherapeutic agents and with higher
spheroid formation efficiency, showing CSC properties. On the other hand, microarray analysis has revealed a number of
differentially expressed genes involved in transcription regulation (e.g. FOXN4, GLI1), immune response (CCR7, IL8) and
transmembrane transport (e.g. ABCC3, ABCC11) in the spheroids. Among these genes, increased expression of CCR7 in
CD44+ CSCs was confirmed in NPC xenografts and primary tumors. Importantly, blocking of CCR7 abolished the sphereforming
ability of C666-1 in vitro. Expression of CCR7 was associated with recurrent disease and distant metastasis. The
current study defined the specific properties of a CSC subpopulation in EBV-associated NPC. Our findings provided new
insights into developing effective therapies targeting on CSCs, thereby potentiating treatment efficacy for NPC patients.